Chandravanshi Lalit P, Yadav Rajesh S, Shukla Rajendra K, Singh Anshuman, Sultana Sarwat, Pant Aditya B, Parmar Devendra, Khanna Vinay K
CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, 226 001, India.
CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, 226 001, India; Department of Criminology and Forensic Science, Harisingh Gour University, Sagar,- 470003, India.
Int J Dev Neurosci. 2014 May;34:60-75. doi: 10.1016/j.ijdevneu.2014.01.007. Epub 2014 Feb 8.
In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC β-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.
鉴于砷对健康影响的发生率不断上升，以及发育中的大脑对其毒性作用的易感性，已开展研究以调查砷诱导胆碱能改变的机制，并了解在停止接触砷后这些变化是持续的还是短暂的。雄性大鼠从哺乳期第22天（PD）至第59天经口暴露于砷（2mg/kg或4mg/kg体重），并在PD60和PD90评估对与胆碱能功能相关的选定行为和神经化学终点的影响。与对照组相比，在PD60时，暴露于砷的大鼠额叶皮质（26%，43%）和海马体（21%，34%）中M胆碱能受体结合减少，同时CHRM2 mRNA水平、乙酰胆碱酯酶活性以及ChAT和PKCβ-1的表达降低。在PD60时，大鼠暴露于砷后，空间学习和记忆以及肌肉力量受到影响，且与砷诱导的胆碱能改变有关。在PD60时，大鼠暴露于砷后，额叶皮质和海马体中均出现与促凋亡蛋白表达增加和抗凋亡蛋白表达降低相关的氧化应激增强。在PD60时，发现胆碱能改变和其他神经化学修饰与额叶皮质（1.39倍，3.90倍）和海马体（3.23倍，5.48倍）中砷水平升高有关。尽管在PD90停止接触砷后，行为和神经化学终点均观察到恢复趋势，但结果表明持续接触砷可能具有有害影响。
